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The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with abnormal activation of the immune system. Recent attention is increasing about how aberrant lipid and cholesterol metabolism is linked together with type I interferon (IFN‐I) signaling in the regulation of the pathogenesis of SL...

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Autores principales: Zhang, Fang, Zhang, Baokai, Ding, Huihua, Li, Xiangyue, Wang, Xilin, Zhang, Xiaomin, Liu, Qiaojie, Feng, Qiuyun, Han, Mingshun, Chen, Longlong, Qi, Linlin, Yang, Dan, Li, Xiaojing, Zhu, Xingguo, Zhao, Qi, Qiu, Jiaqian, Zhu, Zhengjiang, Tang, Huiru, Shen, Nan, Wang, Hongyan, Wei, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520634/
https://www.ncbi.nlm.nih.gov/pubmed/37469011
http://dx.doi.org/10.1002/advs.202207108
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author Zhang, Fang
Zhang, Baokai
Ding, Huihua
Li, Xiangyue
Wang, Xilin
Zhang, Xiaomin
Liu, Qiaojie
Feng, Qiuyun
Han, Mingshun
Chen, Longlong
Qi, Linlin
Yang, Dan
Li, Xiaojing
Zhu, Xingguo
Zhao, Qi
Qiu, Jiaqian
Zhu, Zhengjiang
Tang, Huiru
Shen, Nan
Wang, Hongyan
Wei, Bin
author_facet Zhang, Fang
Zhang, Baokai
Ding, Huihua
Li, Xiangyue
Wang, Xilin
Zhang, Xiaomin
Liu, Qiaojie
Feng, Qiuyun
Han, Mingshun
Chen, Longlong
Qi, Linlin
Yang, Dan
Li, Xiaojing
Zhu, Xingguo
Zhao, Qi
Qiu, Jiaqian
Zhu, Zhengjiang
Tang, Huiru
Shen, Nan
Wang, Hongyan
Wei, Bin
author_sort Zhang, Fang
collection PubMed
description Systemic lupus erythematosus (SLE) is a complex autoimmune disease with abnormal activation of the immune system. Recent attention is increasing about how aberrant lipid and cholesterol metabolism is linked together with type I interferon (IFN‐I) signaling in the regulation of the pathogenesis of SLE. Here, a metabonomic analysis is performed and increased plasma concentrations of oxysterols, especially 7α, 25‐dihydroxycholesterol (7α, 25‐OHC), are identified in SLE patients. The authors find that 7α, 25‐OHC binding to its receptor Epstein–Barr virus‐induced gene 2 (EBI2) in macrophages can suppress STAT activation and the production of IFN‐β, chemokines, and cytokines. Importantly, monocytes/macrophages from SLE patients and mice show significantly reduced EBI2 expression, which can be triggered by IFN‐γ produced in activated T cells. Previous findings suggest that EBI2 enhances immune cell migration. Opposite to this effect, the authors demonstrate that EBI2‐deficient macrophages produce higher levels of chemokines and cytokines, which recruits and activates myeloid cells,T and B lymphocytes to exacerbate tetramethylpentadecane‐induced SLE. Together, via sensing the oxysterol 7α, 25‐OHC, EBI2 in macrophages can modulate innate and adaptive immune responses, which may be used as a potential diagnostic marker and therapeutic target for SLE.
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spelling pubmed-105206342023-09-27 The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus Zhang, Fang Zhang, Baokai Ding, Huihua Li, Xiangyue Wang, Xilin Zhang, Xiaomin Liu, Qiaojie Feng, Qiuyun Han, Mingshun Chen, Longlong Qi, Linlin Yang, Dan Li, Xiaojing Zhu, Xingguo Zhao, Qi Qiu, Jiaqian Zhu, Zhengjiang Tang, Huiru Shen, Nan Wang, Hongyan Wei, Bin Adv Sci (Weinh) Research Articles Systemic lupus erythematosus (SLE) is a complex autoimmune disease with abnormal activation of the immune system. Recent attention is increasing about how aberrant lipid and cholesterol metabolism is linked together with type I interferon (IFN‐I) signaling in the regulation of the pathogenesis of SLE. Here, a metabonomic analysis is performed and increased plasma concentrations of oxysterols, especially 7α, 25‐dihydroxycholesterol (7α, 25‐OHC), are identified in SLE patients. The authors find that 7α, 25‐OHC binding to its receptor Epstein–Barr virus‐induced gene 2 (EBI2) in macrophages can suppress STAT activation and the production of IFN‐β, chemokines, and cytokines. Importantly, monocytes/macrophages from SLE patients and mice show significantly reduced EBI2 expression, which can be triggered by IFN‐γ produced in activated T cells. Previous findings suggest that EBI2 enhances immune cell migration. Opposite to this effect, the authors demonstrate that EBI2‐deficient macrophages produce higher levels of chemokines and cytokines, which recruits and activates myeloid cells,T and B lymphocytes to exacerbate tetramethylpentadecane‐induced SLE. Together, via sensing the oxysterol 7α, 25‐OHC, EBI2 in macrophages can modulate innate and adaptive immune responses, which may be used as a potential diagnostic marker and therapeutic target for SLE. John Wiley and Sons Inc. 2023-07-19 /pmc/articles/PMC10520634/ /pubmed/37469011 http://dx.doi.org/10.1002/advs.202207108 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Zhang, Fang
Zhang, Baokai
Ding, Huihua
Li, Xiangyue
Wang, Xilin
Zhang, Xiaomin
Liu, Qiaojie
Feng, Qiuyun
Han, Mingshun
Chen, Longlong
Qi, Linlin
Yang, Dan
Li, Xiaojing
Zhu, Xingguo
Zhao, Qi
Qiu, Jiaqian
Zhu, Zhengjiang
Tang, Huiru
Shen, Nan
Wang, Hongyan
Wei, Bin
The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus
title The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus
title_full The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus
title_fullStr The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus
title_full_unstemmed The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus
title_short The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus
title_sort oxysterol receptor ebi2 links innate and adaptive immunity to limit ifn response and systemic lupus erythematosus
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520634/
https://www.ncbi.nlm.nih.gov/pubmed/37469011
http://dx.doi.org/10.1002/advs.202207108
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